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The melanocortin 4 receptor (MC4R) is a G protein-coupled receptor (GPCR) that is expressed in several brain nuclei playing a crucial role in the regulation of energy balance controlling the homeostasis of the organism. It displays both agonist-evoked and constitutive activity, and moreover, it can couple to different G proteins. Most of the research on MC4R has been focused on agonist-induced activity, while the molecular and cellular basis of MC4R constitutive activity remains scarcely studied. We have previously shown that neuronal N-type voltage-gated calcium channels (Ca(V)2.2) are inhibited by MC4R agonist-dependent activation, while the Ca-V subtypes that carry L- and P/Q-type current are not. Here, we tested the hypothesis that MC4R constitutive activity can affect Ca-V, with focus on the channel subtypes that can control transcriptional activity coupled to depolarization (L-type, Ca(V)1.2/1.3) and neurotransmitter release (N- and P/Q-type, Ca(V)2.2 and Ca(V)2.1). We found that MC4R constitutive activity inhibits specifically Ca(V)1.2/1.3 and Ca(V)2.1 subtypes of Ca-V. We also explored the signaling pathways mediating this inhibition, and thus propose that agonist-dependent and basal MC4R activation modes signal differentially through G(s) and G(i/o) pathways to impact on different Ca-V subtypes. In addition, we found that chronic incubation with MC4R endogenous inverse agonist, agouti and agouti-related peptide (AgRP), occludes Ca-V inhibition in a cell line and in amygdaloid complex cultured neurons as well. Thus, we define new mechanisms of control of the main mediators of depolarization-induced calcium entry into neurons by a GPCR that displays constitutive activity.

BACKGROUND: The concurrent comparison of questionnaires assessing health-related quality of life in the same population is necessary for better appreciating their performance and to select the best instrument for a given purpose (e.g. clinical trials and observational studies). AIM: The aim of this study was to compare the measurement properties of two disease-specific and generic questionnaires: the Obesity-related Well-Being (ORWELL97), the Obesity-Related Disability test (TSD-OC), the EuroQoL, and the World Health Organization Quality of Life questionnaire. MATERIALS/SUBJECTS: Two-hundreds and forty-nine obese inpatients [age 47 (standard deviation, SD 15) years, body mass index 44.4 (SD 5.2) kg/m(2), 69 % female] completed the four questionnaires before and after a 3-week multidisciplinary weight reduction program. Standard measurement properties were calculated and compared. RESULTS: Intra-class correlation coefficient ranged from 0.73 to 0.90 for most of the instruments and subscales. The standard error of measurement ranged from 9 to 21 % for the generic instruments, and from 9 to 44 % for the specific questionnaires. Missing data and ceiling effects were found for TSD-OC. Responsiveness was similar for all the instruments. The correlations between the change scores of the instruments were small (<0.37). CONCLUSIONS: It was not possible to identify a "best" instrument, but overall the ORWELL97 seems to show better measurement properties. The two specific instruments measured different constructs and they did not show a clear superior performance compared to the generic questionnaires.

The concurrent comparison of questionnaires assessing health-related quality of life in the same population is necessary for better appreciating their performance and to select the best instrument for a given purpose (e.g. clinical trials and observational studies). AIM: The aim of this study was to compare the measurement properties of two disease-specific and generic questionnaires: the Obesity-related Well-Being (ORWELL97), the Obesity-Related Disability test (TSD-OC), the EuroQoL, and the World Health Organization Quality of Life questionnaire. MATERIALS/SUBJECTS: Two-hundreds and forty-nine obese inpatients [age 47 (standard deviation, SD 15) years, body mass index 44.4 (SD 5.2) kg/m(2), 69 % female] completed the four questionnaires before and after a 3-week multidisciplinary weight reduction program. Standard measurement properties were calculated and compared. RESULTS: Intra-class correlation coefficient ranged from 0.73 to 0.90 for most of the instruments and subscales. The standard error of measurement ranged from 9 to 21 % for the generic instruments, and from 9 to 44 % for the specific questionnaires. Missing data and ceiling effects were found for TSD-OC. Responsiveness was similar for all the instruments. The correlations between the change scores of the instruments were small (<0.37). CONCLUSIONS: It was not possible to identify a "best" instrument, but overall the ORWELL97 seems to show better measurement properties. The two specific instruments measured different constructs and they did not show a clear superior performance compared to the generic questionnaires

Argomento di questo articolo è la presentazione dell’Open Philology Project della Humboldt Chair in Digital Humanities dell’Università di Lipsia. Il progetto nasce nell’ambito delle attività del Perseus Project della Tufts University e ha come scopo primario lo sviluppo di una collezione di risorse linguistiche greche e latine leggibili dalla macchina, la creazione di manuali dinamici basati su corpora an- notati e l’avvio di nuove forme di pubblicazione riguardanti le lingue classiche, che possono includere sia annotazioni individuali che edizioni tradizionali integrate con dati elaborabili dalla macchina. L’Open Philology Project include tre componenti principali costituite dall’Open Greek and Latin, dall’Historical Languages e-Learning Project, e dall’Open Access Publishing.